Depression is the most common disabling psychiatric illness and the source of enormous human suffering. Depressive symptoms can be identified in over half of all patients seen in psychiatric practice and it is well known that only a small proportion of those suffering milder forms of depression ever seek medical attention. That depressive features are almost inevitably present in the wake of adverse life situations is accepted as part of the human condition. Depressive symptoms, however, also occur in association with chronic illnesses or as sequelae of both acute and chronic illnesses and injuries, and are often observed in individuals who abuse alcohol, other central nervous system depressants, or narcotics. The Department of Psychiatry (WPIC) of the University of Pittsburgh Medical School in collaboration with the Department of Psychology has proposed the establishment of a MHCRC to investigate the etiology, epidemiology, and treatment of affective disorders. The proposed MHCRC would provide the essential structure and fiscal support to realize the potential for an integrated, multidisciplinary program of investigation, research training, and clinical service. The proposed research program is organized around four major themes: life-span studies of the phenomena of depression (children to the elderly), social and psychological factors in depression, biologic factors in the etiology of depression, and prevention and maintenance treatment studies in affective illness. It should be emphasized, however, that each of the specific proposed investigations is likely to cut across several areas, and thus will provide some of the basis for the communication and collaboration which is fundamental to the MHCRC's goal. Twenty-five specific projects designed to study various facets of depressive illness are detailed in the proposal. All of these projects are either underway or in the preliminary stages of pilot investigation. In addition, a series of new programs of investigation is outlined (including studies in assessment, epidemiology, genetics, clinical psychopharmacology, neurochemistry, psychosocial factors, and neuroendocrinology) which would be developed under the aegis of the proposed MHCRC.